Bacteria-killing sugar

There is a new class of antibiotics: Special sugars that confuse harmful bacteria. The problem with existing antibiotics is that they kill all bacteria, harmful and helpful. The focus of researchers now is on bacteria-specific “narrow spectrum antibiotics”, as opposed to “broad spectrum antibiotics”.

Dr Suvarn Kulkarni of IIT Bombay and Dr Danielle Dube at the Bowdoin College, Maine, USA, have synthesised sugars that pretend to be those that bacteria need to build their own cell walls, but are actually useless for that purpose. So the bacteria do not build a robust cell wall; they actually lose the ability to either attach themselves to the host cells of our body, or proliferate.

These sugars thus effectively halt the growth of disease-causing bacteria.

Antibiotics that target the cell wall growth of bacteria to prevent infection are not new, but this approach, based on the synthesis of sugars for that purpose, is both novel and effective, because they are bacteria-specific.

Bacteria take sugars (monosaccharides) and, with the help of their own proteins (amino acids), assort the sugars into complex structures called ‘glycans’, which adorn their cell walls. Different species of bacteria make different glycans. It is with these glycans that the bacteria attach themselves to our (host) cells.

Thus, if you interfere with the bacteria’s ability to make these glycans, you effectively disarm them.

“Proper assembly of monosaccharides into higher-order glycans is critical for bacterial fitness and pathogenesis,” Kulkarni and Dube say in a paper published in the journal Chemical Science .

Kulkarni and Dube picked up three bacteria for their study — Helicobacter pylori , Campylobacter jejuni and Bacteroides fragilis . The first two are harmful to humans, the third is beneficial. They found out which sugars these bacteria were making. Then they synthesised the same sugars in their lab, but with a small variation. They replaced the ‘hydroxyl’ (OH molecule) in the sugars with either a benzyl group or a fluoro group. This messed with the bacteria’s ability to make glycans. “We tried both (benzyl and fluoro),” Kulkarni told Business Line , “but the fluoro sugar works better.”

Before they did all this, the scientists also added an azide group, or a molecule containing three nitrogen atoms, to these sugars. The azides help in tracking; they could see on which bacteria the synthesised sugars were working.

The results were heartening. The altered rare sugars stumped Helicobacter pylori ; the bacteria grew little and didn’t move much. However, the sugars did not affect Campylobacter jejuni (harmful) or Bacteroides fragilis (beneficial). Conclusion: You have to make sugars specific to the bacteria.

The selectivity (of the synthesised sugars) will provide a pathway for the development of novel, narrow-spectrum antibiotics to treat infectious disease, says Kulkarni. “Our inhibition approach will expedite the identification of bacterial glycan biosynthesis inhibitors in a range of systems, expanding the glycochemistry toolkit.”

Kulkarni said it was a challenge to synthesise fluro-sugars, but they managed it. And now, they are expanding their “arsenal”.

The researchers have synthesised about ten fluorinated rare sugars, and they are making more.

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